Osteoarthritis, also known as degenerative joint disease, is the most common form of arthritis. In addition to man, nearly all vertebrates suffer from osteoarthritis. Osteoarthritis is characterized by damage to and subsequent loss of cartilage in the joints. Cartilage, a slippery connective tissue that is located on the articular surfaces of bones, is necessary for flexibility, support and protection of the bone. When cartilage is damaged due to, for example, injury or stress related to obesity, the joint can no longer function properly and painlessly. When the cartilage deteriorates, osteoarthritis develops.
Early in the progression of the disease, the surface of the cartilage swells and there is a loss of various tissue components, notably proteoglycans. Subsequently, fissures and pits appear on the cartilage and inflammation often occurs around the synovium. As the disease progresses further, the cartilage loses elasticity and becomes more and more susceptible to damage due to continued use and injury. Eventually, much of the cartilage is destroyed, resulting in unprotected bone surface, a condition which is extremely painful.
In an effort to repair the damage, the body often forms fluid-filled cysts around the bony areas or in the regions around the fissures. Local bone cells may respond to the damage by forming dense, misshapen plates around damaged and exposed areas, further limiting joint mobility.
Symptoms of osteoarthritis include pain, stiffness and loss of mobility in one or more joints. Severity of symptoms waxes and wanes with changing weather conditions, advancing disease, and following periods of inactivity.
Osteoarthritis is quite prevalent in the adult population, with over 85% of people over age 65 showing some evidence of the disease upon x-ray. Of these 35%-50% experience symptoms. The causes of osteoarthritis are 1 not completely known, but clearly age, genetic factors, muscle disuse and weakness, trauma, obesity and anatomical abnormalities contribute to the development of the disease. Prevention has focused on weight loss, exercise, hormone therapy such as estrogen replacement in postmenopausal women, and diet supplements such as vitamin D and calcium.
Current treatments are directed primarily towards alleviating symptoms (acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) for pain, hyaluronic acid and exercise to help lubricate the joints, and steroids for inflammation). Surgical alternatives include arthroscopy, resection arthroplasty, osteotomy, chondroplasty and joint replacement.
Clearly, therapies are needed that are less invasive and expensive than surgery and that are directed to correcting the cause—degenerating cartilage, rather than treating a symptom such as pain or inflammation. In accordance with the present invention, Applicants have discovered that a previously described orphan receptor termed ROR2 (see U.S. Pat. No. 5,843,749) appears to play a critical role in cartilage formation and as such may be useful is developing therapeutic strategies to treat diseases of cartilage such as osteoarthritis.